DE102011088874B4 - Apparatus and method for ion mobility spectrometry - Google Patents

Abstract

An ion mobility spectrometer for separating ions according to their ion mobility, comprising a straight drift tube (4) having therein a drift space (22) and at least one spiral guide electrode (70), the drift space (22) having at least two ion separation paths of different lengths, the at least two Ionentrennwege a first Ionentrennweg, which is straight, and a second Ionentrennweg that is spiral, and wherein the at least one spiral guide electrode (70) a switchable voltage for turning on or off of a Leitpotentialbarriere can be applied, so that the ions at turned off Leitpotentialbarriere the straight Ionentrennweg and followed by Leitpotentialbarriere the spiral Ionentrennweg.

Description

Field of the invention

This invention relates to ion mobility spectrometry (IMS) devices and methods, including ion mobility spectrometers. The devices and methods may be suitable for use in combination with mass spectrometry (MS), e.g. In hybrid IMS / MS instruments.

Background of the invention

Known ion mobility spectrometers typically include a drift tube in which ions are caused to drift under the influence of a constant applied electric field. Various designs of the drift tube have been proposed. For example, the drift tube may comprise a series of ring electrodes spaced along the length of the spectrometer, wherein a constant potential difference is maintained between adjacent ring electrodes to produce a constant electric field in the axial direction. An ion pulse is introduced into the drift tube containing a buffer gas, and when the ions pass through the tube under the influence of the constant electric field, they acquire a constant drift velocity and separate in the axial direction according to their ion mobility. The buffer gas is often arranged to flow in the direction opposite to the ion travel direction.

An ion mobility spectrometer may operate on its own as a means of ion separation, or may be used in so-called hybrid IMS instruments in combination with other ion separators. Examples of hybrid IMS instruments include those based on liquid chromatography IMS (LC-IMS), gas chromatography IMS (GC-IMS), and IMS mass spectrometry (IMS-MS). The latter type of instrument is a powerful analytical tool that uses mass spectrometry to further separate and / or identify peaks in an ion mobility spectrum. More than two separation techniques can be combined, e.g. Eg GC-IMS-MS.

Ion mobility spectrometers may be operable at atmospheric pressure (see, eg. US 5162649 A ), and they can provide a resolution of up to 150 (see, for example, Wu et al., Anal. Chem. 1998, 70, 4929-4938). However, operation at lower pressures may be more suitable for hybrid IMS-MS instruments (see, eg. US 5905258 A and WO 01/64320 A1 ) to increase the separation speed and reduce ion losses. Operation of the ion mobility spectrometer at lower pressures often results in greater diffusion losses and lower resolution. To address the problem of diffusion losses, an RF pseudopotential well could be placed in the drift tube to radially confine ions so that it acts as an ion conductor and can be used to efficiently transport ions (see, eg, US Pat. US 6630662 B1 ).

In a modification of an ion mobility spectrometer describes US 6914241 B2 how ions can be separated according to their ion mobility by the progressive application of transient DC voltages along the length of an ion mobility spectrometer or RF ion guide having a plurality of axially spaced electrodes. The ion mobility spectrometer may include an RF ion guide, such as a multipole rod set or a stacked ring set. The ion conductor is segmented in the axial direction so that independent transition DC potentials can be applied to each segment. The transient DC potentials are superimposed on an RF voltage which serves to radially confine the ions and / or any constant DC offset voltage. The transient DC potentials thereby produce a so-called traveling wave that moves along the length of the ion conductor in the axial direction and has the effect of moving ions along the length of the ion mobility spectrometer.

In the above types of ion mobility spectrometers, ions are driven along the ion guide and the ions can be separated according to their ion mobility. However, in order to obtain high resolution or resolution performance of ion mobility separation at relatively low pressures, a relatively long drift tube must be used to comply with the so-called low field limit, as described in more detail below.

To separate ions along the axial direction according to their ion mobility in an RF ion guide, an axial DC electric field orthogonal to the RF radial field could be generated for radial confinement. When a constant axial electric field E is applied to ions along and move through a gas-containing ionic conductor, then the ions acquire a characteristic velocity v according to: v = E · K (Equation 1) where K is the ion mobility.

wobei z der Ladezustand der Ionen ist, L die Trennungslänge (m) ist, T die Temperatur (Grad Kelvin) des Hintergrundgases ist, e die Elementarladung (1,602·10^–19 Coulomb) ist und k die Boltzmann-Konstante (1,38·10^–23 J/K) ist. Genauere Berechnungen kann man zum Beispiel finden in G. E. Spangler, „Expanded Theory for the resolving power of a linear ion mobility spectrometer”, Int. J. Mass Spectrom. 220 (2002) 399–418. Da die Zunahme von E durch die Niedrigfeldbedingungen beschränkt ist und die Abnahme von T mit mühseligen kryogenen Techniken einhergeht, kann man ersehen, dass der einzige Weg zum Erlangen von höherem R ist, die Trennungslänge L zu vergrößern. Jedoch kann die Vergrößerung der Trennungslänge problematisch sein, da Platz typischerweise beschränkt ist.In order to comply with ion mobility separation in the so-called low field regime wherein ions do not receive significant kinetic energy from the driving field, the ratio of E (in V / m) to background gas pressure P (in mbar) should be less than about 200V / (m · mbar) are kept. At the same time, the dissolving power, R, of ion mobility separation (FWHH) is limited by diffusion and can be estimated approximately as:

where z is the state of charge of the ions, L is the separation length (m), T is the temperature (degrees Kelvin) of the background gas, e is the elementary charge (1.602 · 10 ^-19 Coulomb) and k is the Boltzmann constant (1.38 x 10 ^-23 yr / K). More detailed calculations can be found, for example, in GE Spangler, "Expanded Theory for the Resolving Power of a Linear Ion Mobility Spectrometer", Int. J. Mass Spectrom. 220 (2002) 399-418. Since the increase of E is limited by the low field conditions and the decrease of T is associated with cumbersome cryogenic techniques, it can be seen that the only way to obtain higher R is to increase the separation length L. However, increasing the separation length can be problematic because space is typically limited.

A solution to the problem of increasing the separation length, which in the prior art of WO 2008/104771 A1 . GB 2447330 A and GB 2457556 A It is proposed to wind up the ion mobility drift tube. However, in this case, the construction of the drift tube is complex and precludes the rapid transfer of ions through the spectrometer in the event that mobility separation is not required.

For the sake of completeness, please also refer to DE 197 30 896 A1 and the GB 2 457 556 A directed.

It can therefore be seen that there is a need to improve ion mobility spectrometers, in particular a need to provide an ion mobility spectrometer with increased separation length, and more particularly a need to provide an ion mobility spectrometer with increased separation length but without complex construction. In view of the above background, the present invention has been accomplished.

Summary of the invention

According to one aspect of the present invention, there is provided an ion mobility spectrometer for separating ions according to their ion mobility according to claim 1.

According to another aspect of the present invention, there is provided a method of separating ions according to their ion mobility according to claim 17.

Preferably, the at least two ion separation paths are adjacent to electric field generation means, wherein the electric field generation means are switchable between operating states to provide in one state an electric separation field substantially aligned with a first path of a first length and in one another state to provide a different electrical separation field, which is substantially aligned with a second path of a second length, which is different from the first length.

According to the invention, the ion mobility spectrometer for separating ions according to their ion mobility has a straight drift tube having therein a spiral ion separation path.

According to claims 1 and 17, the at least two ion separation paths with different lengths of the ion mobility spectrometer comprise a first ion separation path which is straight and a second ion separation path which is spiral. More preferably, the second ion separation path is longer than the first ion separation path.

Advantageously, the present invention addresses the problem of how to increase the ion mobility separation length within a limited space and with a simple construction. It will be appreciated that the invention, in certain embodiments, provides at least two ion separation paths (i.e., ion trajectories) within a drift tube containing an ion separation path that is a spiral ion separation path. This construction allows various special operating modes. In an ion separation path, for example, the curved or spiral path, a long separation path with high ion mobility and low-speed dissolution performance may be provided. The at least one other path is straight and is a shorter separation path with lower ion mobility resolution and speed than the spiral path. The present invention thus provides an ion mobility spectrometer having at least two ion separation paths of different lengths, thereby enabling at least two different resolution powers and two different separation speeds, particularly in the low field regime for the axial electric field. The invention accordingly provides an ion mobility spectrometer and a method for ion mobility spectrometry with switchable speed and / or resolution modes. The drift tube itself is straight, unwound and at least has a simple construction compared to prior art screwdriving drift tubes.

The drift tube is a straight drift tube and it is advantageous to obtain a high dissolution performance through a spiral ion separation path within a straight drift tube wherein the drift tube has a similar length to a conventional straight drift tube, the length of the spiral ion separation path being substantially longer than the length of the drift tube drift tube. The invention thus enables a long separation path length, and therefore, in a limited space, a high resolution of ion mobility separation can be achieved.

In certain preferred embodiments, the present invention contemplates filtering ions according to ion mobility, and coupling the filtered ions into another ion separation and / or identification device, preferably a mass spectrometer.

Other advantages of the present invention include the possibility of rapid ion transfer through the ion mobility spectrometer when mobility separation is not required. This could be used in combination with further mobility separation, for example, to add internal calibrants to the mobility-selected species.

Typically, ions to be separated by the ion mobility spectrometer of the present invention are generated by an ion source, which will be described below. The generated ions may be injected into the ion mobility spectrometer through an injection device having, for example, ion optics, which may include, for example, an injection multipole.

The ion mobility spectrometer may include an ion storage device or an ion storage section into or into which the ions to be separated may be introduced, for example, the ion source, wherein the ion storage device or the ion storage section has an ion storage site therein. The ion storage device or the ion storage section may preferably have an ion trap. The ion storage device or the ion storage section preferably serves for the controllable storage of the ions and the release of the ions into the drift tube of the ion mobility spectrometer for separation, preferably as an ion pulse, ie. that is, it is preferably a pulsed ion storage device or a pulsed ion storage section. The ion storage device or the ion storage portion is preferably configured to provide an axial field gradient in the ion storage space when a voltage difference is applied between the axial ends thereof. The axial field gradient in the storage space can thereby move ions in the storage location in the axial direction to the drift tube of the ion mobility spectrometer for separation. Ions may be stored in the storage device or storage section until injection into the drift tube is required. Thus, preferably, the ion storage device or the ion storage section allows the controllable sluice of ions into the drift tube, for example by means of an inlet electrode. It can be seen from the above preferred embodiments that the ion mobility spectrometer preferably comprises a pulsed ion injector, which may be provided, for example, by the described ion storage device, for pulsed injection of ions into the drift tube.

The ion mobility spectrometer comprises a drift tube having separation paths therein. The drift tube defines therein a drift space in which the ions can be separated according to ion mobility. The drift space preferably contains a gas for ion mobility separation.

The drift tube thus contains a drift space in which the at least two ion separation paths are provided. The first ion separation path is straight, and particularly preferably runs in the axial direction through the drift space. The second ionic separation path is spiraled according to claims 1 and 17, most preferably the axis of the spiraling path is substantially coaxial with the longitudinal axis of the drift tube. The longitudinal axis is preferably radially in the middle of the drift tube. For axial movement of ions, an axial electric field gradient (an axial DC field) is preferably applied in the drift tube in use. The axial electric field gradient may be generated, for example, by a DC voltage difference applied between the axial ends of the drift tube.

The drift tube is straight. It is understood that herein "straight" means at least substantially straight, and some deviation from a strictly geometrically straight configuration is thereby permitted. The drift tube particularly preferably comprises an axially extending outer tube. The drift tube preferably includes an axially extending outer electrode assembly that defines the drift space therein. Thus, in certain embodiments, the outer electrode is preferably the outer tube. The outer tube or the outer electrode particularly preferably has the shape of a cylinder. The outer electrode has a resistance material that is at least on the inner surface. Particularly preferably, the outer electrode is made of resistance glass. In use, where the outer electrode is a resistive material, it is preferred to apply a voltage between the axial ends of the outer electrode to create a voltage gradient in the axial direction that can thereby promote movement of the ions from the axial entrance end of the drift tube to the axial exit end. d. h., to favor the axial movement of the ions. In other embodiments, alternatively or in addition to the outer electrode, which provides an axial voltage gradient, an axial voltage gradient may be provided from the inner electrode, for example from the inner electrode alone. Providing an axial voltage gradient through the inner electrode will be described in more detail below.

The ion mobility spectrometer preferably includes an axially extending internal electrode assembly disposed within the drift tube. Preferably, the outer electrode or the outer tube surrounds the inner electrode assembly in an annular manner. The drift space is arranged in these embodiments between the outer tube or the outer electrode of the drift tube and the inner electrode assembly, d. H. annularly around the inner electrode assembly. The inner electrode assembly is preferably disposed within the outer tube or the outer electrode coaxial with the outer tube. The inner electrode assembly particularly preferably has a cylindrical shape. Accordingly, the drift tube very particularly preferably comprises two coaxial cylinders, wherein the drift space is arranged between the coaxial cylinder, the cylinders having an outer cylinder as outer electrode and an inner cylinder as inner electrode assembly. The spiral Ionentrennweg is thus arranged in these embodiments in the drift space between the coaxial cylinders and rotates around the inner cylinder.

In use, the ions are moved axially through the drift space in the drift tube by means which will be described in more detail below. As the ions move through the drift space, they are separated according to ion mobility. When the ions are moved axially, the ions are preferably confined radially. In use, the ions are preferably confined radially by means of an electric RF field. In addition, for radial confinement in the drift tube in use, a radial electric field gradient (a radial DC field) is further applied, e.g. B. by a DC voltage difference, which is applied between the outer electrode of the drift tube and the inner electrode assembly, wherein z. For example, ions are driven toward the inner electrode assembly by a DC voltage difference applied between the outer electrode of the drift tube and the inner electrode assembly. For the radial RF field, the drift tube preferably comprises one or more RF electrodes for radially confining the ions by applying the RF radial field. The RF electrodes generate an RF barrier that counteracts the radial alignment effect of the DC voltage difference, which is e.g. B. between the outer electrode of the drift tube and the inner electrode assembly is applied. The RF electrodes, in some embodiments, may have a combination of DC and RF applied thereto to produce both the radial DC field gradient and the RF radial field. In a preferred embodiment, the inner electrode assembly preferably includes RF electrodes spaced annularly about the central axis (ie, the longitudinal axis) of the drift tube extending axially, preferably parallel to the longitudinal axis, ie, in the axial direction. The RF electrodes are preferably arranged at the same distance annularly around the center (longitudinal axis) of the drift tube around. For example, the HF Electrodes may be arranged annularly around the inner electrode assembly (but separated therefrom), ie with the ion separation paths, which are arranged radially outside the RF electrodes. The RF electrodes to which at least one RF voltage is applied in use thereby create an RF barrier to prevent ions from colliding with the internal electrode assembly, e.g. Where the voltage differential applied between the outer electrode of the drift tube and the inner electrode assembly drives the ions toward the inner electrode assembly. Additionally or alternatively, the RF electrodes can be equally spaced annularly adjacent to (but separated from) the inner surface of the outer electrode assembly, thereby creating an RF barrier in use when RF is applied to prevent ions from interfering with the outer Collide electrode assembly, z. Where the voltage differential applied between the outer electrode of the drift tube and the inner electrode assembly drives the ions toward the outer electrode assembly. The RF electrodes may preferably comprise wires. In use, adjacent pairs of the RF electrodes are preferably provided with antiphase RF voltages. From the foregoing, it will be appreciated that, in use, ions in the drift tube can be radially confined by applying a radial DC field in combination with an RF field in the drift tube applied by one or more RF electrodes connected to the inner electrode assembly and / or the outer electrode assembly are coupled.

In another preferred embodiment, ions in the drift tube are radially confined by applying an RF field to the entire internal electrode assembly to thereby create a quasi potential in the drift tube, the RF field having the internal electrode assembly by means of one or more RF electrodes coupled within the internal electrode assembly. Similarly, the RF field could be coupled to the outer electrode assembly, thereby creating a quasi-potential in the drift tube by means of an RF electrode or RF electrodes located in proximity to the outer electrode assembly. The overall combined effect of the radial field effects described above is such that in the drift tube there is a radial electric field with a potential minimum at a radius within the drift space, thereby providing a radial confinement to the potential minimum.

The switchable electric field generating means comprise one or more electrodes, as described below.

The ion mobility spectrometer, in use, preferably includes an axial electric field to drive the ions axially in the drift tube, i. H. along the longitudinal axis of the drift tube. For this purpose, the ion mobility spectrometer preferably comprises an axial drive electrode, which is preferably a resistance electrode for exerting an axial drive force on the ions, i. to drive the ions axially in the drift tube. The axial drive electrode may be continuous or segmented. In particular, when the axial drive electrode is segmented, it need not have resistance, but may be made of conductive material with stepped voltages applied between successive segments to produce an axial electric field. The axially driving electrode may be linear, or more preferably spiral, as described in more detail below, in each case extending in the axial direction. In some embodiments, the outer electrode of the drift tube, which may have a resistance, forming the axial drive electrode, at least partially. Where the axial drive electrode is helical, it preferably extends axially along the drift tube, with the axis of the helix that forms it being substantially coaxial with the longitudinal axis of the drift tube.

The ion mobility spectrometer preferably comprises at least one guide electrode for generating a conduction potential barrier for directing the ions along a path other than a straight path, e.g. B. steer ions along a spiral path. Accordingly, the lead electrode according to claims 1 and 17 is a spiral electrode. The sparse path created by the baffle is longer than a straight path through the drift tube and, accordingly, as the ions follow the path created by the baffle, they are separated with higher resolution than if they followed a straight path through the drift tube. The spiral guide electrode preferably extends axially along the drift tube, with the axis of the helix that forms it being particularly preferably coaxial with the longitudinal axis of the drift tube. The guide electrode may be continuous or segmented. The guide electrode is used according to claims 1 and 17 for applying a switchable voltage thereto, in order to turn on or off the Leitpotentialbarriere can. This feature advantageously allows two separation paths to be provided in the drift tube, e.g. A path where the conductive potential barrier is off (the straight path), and a path where the conductive potential barrier is on (the spiral path). If both are present, the spiral axial drive electrode and the spiral guide electrode are arranged to form a double helix, and preferably the axis of the double helix is substantially coaxial with the longitudinal axis of the drift tube. In In certain preferred embodiments, the spiral guide electrode is wrapped around the inner electrode assembly. The conducting electrode may be conductive or with resistance, preferably with resistance.

The inner electrode assembly further preferably comprises an inner support, in particular a cylinder, which particularly preferably extends axially along the length of the drift tube. This inner support or cylinder is preferably made of dielectric material. The inner support or cylinder preferably carries therein the axial drive electrode and / or the lead electrode as described above and in more detail below. However, in certain embodiments, the outer cylinder may additionally or alternatively bear thereon (eg, on its inner surface) an axial drive electrode and / or a lead electrode, as described above and in more detail below.

Preferably, particularly for use in high resolution separation modes, the spectrometer includes arcuate field electrodes, which preferably extend axially along the drift tube and are disposed about the longitudinal axis of the drift tube, i. H. arcuately spaced around the longitudinal axis. The electrodes for an arcuate field are preferably arranged at the same distance arcuately around the longitudinal axis. The electrodes for an arcuate field may preferably be provided in the form of conductive strips. The arcuate field electrodes may be provided on the inner surface of the outer tube and the outer electrode of the drift tube or on the outer surface of the inner electrode assembly. The electrodes for an arcuate field preferably extend parallel to one another, particularly preferably when they extend axially. In use, preferably, a switchable voltage is independently applied to each electrode for an arcuate field to thereby produce a arcuate electric field. The arcuate field is a rotating and not a static field, which is obtained by progressively applying the independent switchable voltages to the electrodes for an arcuate field, i. H. in the form of a transient waveform.

At the exit of the drift tube, ie after the ions have been separated according to ion mobility, the separated ions are extracted from the drift tube, e.g. Via an output gate electrode to allow pulsed extraction. After the ions are extracted, they may proceed to one or more further stages of ion processing (eg, mass spectrometry, such as mass filtering, ion storage, and / or mass analysis, with or without ion fragmentation) and / or detection. For example, various hybrid instrument configurations may include the ion mobility spectrometer of the present invention, such as IMS / MS or IMS / MS / MS or IMS / (MS) ⁿ , where IMS denotes a stage of ion mobility spectrometry of the present invention and MS a stage of mass spectrometry.

The ion mobility spectrometer of the present invention can be operated in different modes.

In an operating mode, called a pass-through mode, the ions are drifted through the drift tube by being pulled off the axial field, but without ion mobility separation. In other words, in this transmission mode, the spectrometer thus acts as a simple ion conductor.

In a low resolution ion mobility separation mode of operation that can achieve resolution of ion mobility separation similar to existing grade-path ion mobility spectrometers, the spectrometer operates in pass-mode, except that the ions are preferentially injected as a pulse into the drift tube and ions are separated for ion mobility. when they walk through the drift tube. In this low-resolution mode, the voltage of the lead electrode is turned off or set low so that there is substantially no potential barrier affecting the axial movement of the ions. Accordingly, in this low resolution ion mobility separation mode, the ions axially drift substantially straight through the drift tube.

In a high resolution mode of operation for ion mobility separation, the high resolution mode uses the lead electrode to provide a longer pathway separation path, ie, higher resolution performance, according to claims 1 and 17, a spiral pathway. In the high resolution mode, as in the low resolution mode, the ions are preferentially injected as a pulse into the drift tube and the ions are separated for ion mobility as they travel through the drift tube under the influence of the axial electric field gradient. The voltage of the conductive electrode is turned on so that there is an electric potential barrier which limits the pure axial movement of the ions and instead the ions must follow the potential barrier which is spiral based on the spiral conductive electrode. The high resolution mode is preferably operated with a rotating arcuate electric field applied in the drift tube. Accordingly, the arcuate field electrodes are preferable in this Mode are operated so that voltages are applied to them progressively independent to generate a rotating arcuate electric field (ie, a field in the arc or angular direction) to drive ions within the arcuate electric field in the arc direction. The rotating arcuate electric field is preferably provided to have a sector (ie, in the arc direction) of less than 360 °, e.g. B. 240 °, spans. This can be achieved by applying suitable voltages, preferably substantially the same voltage, to two of three equally arc-spaced electrodes for an arcuate field, with another or no voltage on the one remaining of the strip. The rotational velocity (ie, in the arc direction) of the rotating arcuate field is preferably synchronized with the rotational velocity of ions of a selected ion mobility K such that the rotating arcuate field and the ions of the selected ion mobility are in phase so that these ions travel through the drift tube helical path, whereas ions of another ionic mobility become out of phase with the arcuate field and thus can be slowed or lost in the spectrometer. This rotating electric field can be used to provide a filtering effect so that only ions of a selected ion mobility are transmitted through the spectrometer while other ions are filtered out. In the high resolution filtering mode, the electric field in the sector outside the rotating arcuate field is preferably a defocusing field, so that ions in this remaining sector are lost on a wall of the drift tube. The defocusing field can z. B. are generated by a radial DC field gradient, which aligns ions so that they are lost to a wall of the drift tube. The high resolution mode may alternatively be operated with trapping, so that ions whose rotational speed is slower or faster, ie out of phase, than the rotating arcuate electric field, nevertheless remain trapped in the drift tube. The trapped ions can remain trapped in the drift tube, e.g. By a radial DC field gradient in the remaining sector which guides ions to remain within the drift tube, e.g. Until the rotational speed of the arcuate field is changed to match the rotational velocity of the trapped ions, and therefore the trapped ions can be transmitted through the drift tube.

The duty cycle of the ion mobility spectrometer can be increased by injecting ions into the ion mobility spectrometer with the same phase of subsequent cycles of the rotating arcuate field, most preferably each subsequent cycle of the rotating arcuate field.

In one mode of operation, a mass spectrometer may be configured to detect ions extracted from the ion mobility spectrometer with selected ion mobility having one or a limited number of m / z values, thereby rendering the instrument an ion specific detector. In a particularly typical mode of operation, a mass spectrum is obtained by a mass spectrometer for each of a plurality of narrow ranges of ion mobilities transmitted by the ion mobility spectrometer (ie, a mass spectrum is obtained for each ion mobility peak, thereby forming a single ion mobility peak in its m / z components dissolve). A two-dimensional (2D) mobility / mass diagram can be obtained in this way. Another preferred method is a so-called coupled scanning method that allows selection only of ions of a particular type or types, e.g. Peptides only, which can greatly enhance the dynamic range of analysis of complex mixtures and avoid the analysis of analytically useless ions (eg, singly charged and polymer ions in the case of peptide mixtures). In the coupled scanning method, a mass filter, for. For example, a quadrupole mass filter located downstream of the ion mobility spectrometer is scanned concurrently with the mobility scan by the ion mobility spectrometer, so that only ions of the predetermined mobility / mass ratio or those that are at a predetermined curve on a mobility / mass plot will follow Editing or detection are selected, for. B. mass analysis, with or without interfragmentation of the selected ions. The selected ions of predetermined mobility / mass ratio or those lying on a predetermined curve on a mobility / mass diagram are thus preferably accumulated in an ion trap before being subjected to the subsequent mass analysis, e.g. By an FT mass analyzer that measures the oscillation frequency induced by a potential that varies harmonically in one direction (eg, an Orbitrab ^™ mass analyzer) or a TOF mass analyzer. The space charge capacity of the ion trap can be fully utilized since only ions of interest are selected and accumulated in the trap. In such an operation, a high resolution mass spectrum can be obtained when obtained with, for example, an Orbitrab ^™ analyzer containing only ions of interest (eg, two- or three-charged ions or only glycopeptides, etc.), and therefore fully exploited the space charge capacity of the trap or analyzer. One or more scans may be made on different mobility / mass ratios or on different curves on a Mobility / Mass Diagram.

It is understood that the spectrometer of the present invention may be suitable for the transfer and separation of either positively or negatively charged ions. The voltages applied to the various electrical components need only be reversed in their polarities to pass and separate ions of opposite porosity.

It is understood that further modifications can be made to the present invention incorporating features of ion mobility spectrometers of the prior art. For example, according to certain embodiments of the present invention, an arcuate field is used that rotates, ie, is applied as a so-called traveling wave. The feature of applying an axial field gradient as a traveling wave for further filtering the ions according to their ion mobility, as in the prior art (eg. US 6914241 B2 ) can also be used. For this purpose, the axial field gradient or the axial drive electrode preferably has a segmented shape so that potentials can be applied progressively to successive segments, thereby creating an axial traveling wave field gradient.

Detailed description of the invention

To better understand the invention, it will now be described, by way of example, with reference to the accompanying drawings, in which:

1 Fig. 2 shows schematically a side view, partly in cross-section, of an embodiment of an ion mobility spectrometer according to the present invention, taken along the line BB in Fig. 1 2 ;

2 schematically shows a cross-sectional view of in 1 shown embodiment along the line AA;

3 shows a DC profile in the axial (z) direction within the ion spectrometer in one embodiment of the operation;

4 shows the DC profile in the arc or angle (φ) direction within the ion mobility spectrometer in one embodiment of the operation;

5 shows potential profiles in the radial direction for a sector in phase with an applied arcuate electric field in a high resolution filtering embodiment;

6 shows potential profiles in the radial direction for a sector out of phase with an applied arcuate electric field in a high resolution filtering embodiment;

7 schematically shows an embodiment of a hybrid IMS / MS / MS instrument incorporating an ion mobility spectrometer according to the present invention;

8th shows a two-dimensional (2D) mobility / mass diagram that can be obtained by means of an embodiment of the present invention;

9 shows a coupled scanning method that can be performed by one embodiment of the present invention, thereby scanning ions of a set mobility / mass ratio;

10 shows a similar view 1 another embodiment according to the present invention; and

11 Fig. 12 schematically shows a cross-sectional side view of another embodiment of an ion mobility spectrometer according to the present invention.

In the 1 and 2 are schematic, and therefore not to scale, a partially sectioned side view and a cross-sectional view of an ion mobility spectrometer 2 shown according to the present invention. The 1 and 2 show the directions of the polar coordinates, z, r and φ.

From the spectrometer 2 ions to be separated are generated by an ion source (not shown), which may be any suitable ion source and which may also be a conventional type of ion source, e.g. An electrospray ionization (ESI) source, a matrix-assisted laser desorption ionization (MALDI) Source or any other type of ion source. The ions generated by the source may be present in the spectrometer 2 be introduced by means of an injection device, which typically contains an ion optic, which in the embodiment shown, a Injektultmultipol 10 having. In other embodiments, the injection device could include any RF transmission or RF storage device, such as an elongated set of rods, orifices, coils with or without a gas bath. The ions injected by the injection device enter the spectrometer via an access port 20 one. The entrance opening 20 acts as an ion gate and one can apply a switchable voltage to selectively pass either ions (gate open) or not pass (gate closed).

The spectrometer 2 includes a drift tube 4 which in the embodiment has an outer electrode, in this case in the form of a cylinder 30 elongated in the axial direction, z, which is the longitudinal axis of the tube. In 1 is the cylinder 30 shown in axial cross section. The length of the cylinder 30 is in this embodiment 200 mm and its inner diameter is 60 mm. The cylinder 30 is how in 2 shown, a circular cylinder, but it does not need to be. The cylinder could z. B. also have any other cross-sectional shape, such as elliptical or any other curved shape, although a circular cylinder is preferred. The electrode cylinder 30 is manufactured in this embodiment of resistance glass, but could also be made of any other resistance material. Resistance glass drift tubes for ion mobility spectrometers are known per se. In other cases, the cylinder could run 30 have a resistance material only on its inner surface. When in use, a voltage of 50-200 V between the ends of the cylinder 30 (ie, its opposite axial ends) is thus created, a voltage gradient in the axial direction is generated, which can support the movement of ions from the input end of the drift tube to the output end, ie, the axial movement of the ions.

The spectrometer of the illustrated embodiment comprises a storage section 30 ' , the electrically insulated section of the resistance cylinder 30 or another cylinder having resistance material (at least on its inner surface) of the same diameter and coaxial with the cylinder 30 , and electrically isolated from the main part of the cylinder 30 in which the separation of the ions takes place. In other embodiments, however, as described in the following 11 shown, the storage portion to have no coaxial cylinder, coaxial with the master cylinder 30 of the drift tube, since the storage section only has to provide an area for storing ions before the ions, preferably as a pulse, enter the drift tube 4 be released. The ions from the injection device initially enter the storage section 30 ' over the opening 20 one. The storage section 30 ' defines a memory space 21 which, in this example, is an annular storage space (although, as stated above, it need not be annular, for example in cases where the storage portion does not have a coaxial cylinder) in which the ions can be stored before ions pass through in the separation section of the cylinder 30 ie in the drift space 22 , to be selected. The storage section 30 ' preferably comprises resistive material, at least on its inner surface, and carries in electrical connection therewith two electrodes, in these examples in the form of annular conductive strips 31 . 32 , each at each end of the memory section 30 ' are provided to generate an axial electric field gradient when between the electrodes or strips 31 . 32 , in this example ring-shaped electrodes, a voltage difference of 5-50 V is applied. In use, the ions move in the axial direction to the separating portion of the cylinder 30 under the influence of the axial gradient in the storage section 30 ' , The ions can in the memory section 30 ' be held and controllable in the separating section of the cylinder 30 by means of a voltage applied to a lock electrode described in more detail below 61 is created.

In the outer cylinder 30 of the spectrometer is an internal electrode assembly 40 arranged. The electrode assembly 40 is coaxial with respect to the outer cylinder 30 appropriate. The drift room 22 in which, in use, the ions are separated by ion mobility, the annular volume between the outer cylinder comprises 30 and the inner electrode assembly 40 , The drift room 22 is filled with gas in use. The gas may be any gas conventionally used for ion mobility spectrometry (such as nitrogen, helium, methane, etc., or any mixture thereof). The gas may have pressures in the drift space known to be useful in ion mobility spectrometry technology, e.g. B. atmospheric pressure or super or subatmospheric pressure. However, the gas is preferably at atmospheric pressure or below. More preferably, the gas is at atmospheric pressure, most preferably 0.005 to 20 mbar, and most preferably 0.1 to 1 mbar. The gas may be intended to flow in the drift space, e.g. B. against the direction of ion movement, but preferably and for simplicity, because you can not flow the gas.

The electrode assembly 40 includes RF electrodes 50 at the same distance annular around the z or longitudinal axis of the drift tube around and parallel to the z-axis, ie the axial direction, extend. In the Execution are the HF electrodes 50 expediently provided in the form of wires, via holders 53 . 54 are curious. In use, adjacent wires, e.g. B. shown as 51 . 52 , provided with antiphase RF voltages to produce an RF quasi potential. In 2 each wire is provided with the same hatch with the same phase of the RF voltage. The HF electrodes 50 thereby create an RF barrier to prevent ions from entering the electrode assembly 40 to fall. The ions are radially confined in use by being separated from one between the outer cylinder 30 and the electrode assembly 40 Apply a DC difference of 1 to 20 V to the inner electrode assembly 40 and their RF barrier are pushed out.

The electrode assembly 40 further comprises an inner cylinder 60 which runs the length of the spectrometer and the drift tube. The cylinder 60 is preferably made of dielectric material, preferably glass (eg lead silicate) or ceramic. The outer diameter of the cylinder 60 is 50 mm. The inner cylinder 60 has the effect of both a lock electrode, in this case in the form of an annular conductive strip 61 and a conductive electrode, in this case in the form of a resistor strip 70 spiraling around the cylinder 60 wrapped around, to carry. In the embodiment shown, the inner cylinder carries 60 an axial drive electrode, in this case in the form of a resistor strip 62 , which also spirals around the cylinder 60 wrapped around. For the sake of simplicity, in the cross-sectional view of 2 , neither resistance strips described below 70 still the resistance strip 62 shown. The annular conductive band 61 surrounds the circumference of the cylinder 60 and is at the output of the memory space 21 arranged axially. In the embodiment shown, the annular conductive band 61 with the conductive strip 62 positioned axially in height. When in use, a switchable gate voltage is applied to the annular conductive tape 61 is applied, this acts as a lock electrode to ions from the storage space 21 in the drift room 22 to pass, whereby the ions are separated according to the ion mobility. To the annular conductive band 61 Thus, a switchable voltage is applied to selectively allow either ions to pass (gate open) or not to pass (gate closed). The resistance strip 70 is spiraling around the cylinder 60 around with the axial direction along the length of the cylinder 60 wound. The resistance strip 70 serves for applying a switchable DC voltage. If at the resistance strip 70 A voltage is applied thereby creating a spiral potential barrier for the axially moving ions, as described in more detail below. The conductive strips or components described herein are preferably made of metal, such as e.g. As nickel, tungsten or gold. The resistance stripes 62 and 70 are preferably prepared by hydrogen reduction of lead silicate glass, as known in the art, or by chopping (sputtering) ultrathin layers of tungsten or other resistive metals onto glass or ceramic. It is also conceivable to produce strips by injection molding of conductive plastic, such as Sintimid, Tecaform, Semitron and others.

The inner cylinder 60 also carries a resistance strip 62 that also spirals around the cylinder 60 wrapped around. The resistance strip 62 is in the axial direction along the length of the cylinder 60 spiral around the cylinder 60 wrapped around. The spiral of the resistance strip 62 and the spiral of the resistance strip 70 are arranged in the embodiment to form a double helix configuration, ie, they are two congruent spirals. The spiral of the resistance strip 62 and the spiral of the resistance stiffener 70 thus have essentially the same pitch of 10 mm, resulting in 20 turns along the drift tube 4 results (not all turns are shown in the schematic figures). The spiral of the resistance strip 62 and the spiral of the resistance strip 70 are preferably in relation to each other, approximately half way along the spiral pitch, offset in the axial direction. The radius of a spiral (or both) is preferably constant, but could vary to provide one or more sections to increase or decrease the radius along the axial direction, thereby creating a spiral configuration. Accordingly, as used herein, the term spirally and similar terms, such as helix, refers to either a strictly spiral, fixed radius, or a spiral of increasing and / or decreasing radius.

Typically, the pitch or axial pitch of the spiral is several times greater than the gap between the cylinder 60 and the RF electrodes or wires 50 , The slope or axial step of the spiral is thus typically with the gap between the outer cylinder 30 and the inner electrode assembly 40 comparable. For example, for a gap of 5mm between the inner cylinder 40 and the outer cylinder 30 and a diameter of 50 mm of the inner cylinder 40 increase the separation length> 15 to 30, compared to the low-resolution mode, and therefore in the resolution, a gain x4 to x5. This is obtained from dimensions of the spiral pitch P = 10 mm, diameter D = 50 mm of the cylinder 40 and the total length of the tube, L = 200 mm, so that the increase in the separation length over L is equal to π · D / P = 15.7, with a total length of 3.14 m.

The resistance strip 62 Used to apply a switchable voltage of 20 to 500 V to it. A similar stress distribution is applied to the strip 70 but shifted by 2 to 20 V, according to the polarity of the ions (high for positive, down for negative). If at the resistance strip 62 a voltage is applied, thereby an axial electric field gradient is generated along this, and in the drift space 22 An axial electric field is generated to move the ions axially through the drift space 22 to move, as described in more detail below. As the resistance strip 62 is used to generate an axial field gradient to move the ions axially through the drift space 22 To move, it is possible to use a resistance strip that has a slightly different configuration than spiral. For example, the resistor strip could 62 in some embodiments, be in the form of a straight strip that extends in the axial direction along the inner cylinder 60 runs. Such an embodiment is in 10 shown ( 10 also shows the memory section 30 ' as part of the cylinder 30 ). However, with regard to the spiral resistance strip 70 , the resistance strip 62 preferably spirally and more preferably forms a double helix with the resistance strip 60 , When the resistance strip 62 is spiral, not axial (ie arcuate) field components through the resistance strip 70 and also the electrodes for an arcuate field 33 - 35 dominated.

In addition to the spiral strip 70 to exert a further driving force on the ions in the angular direction, and in particular for use in high resolution separation modes, the spectrometer electrodes for an arcuate field, in this case in the form of conductive strips 33 . 34 and 35 attached to the inner surface of the outer cylinder 30 of the drift tube 4 available. The conductive stripes 33 . 34 and 35 are made of conductive material and extend parallel to each other, axially along the length of the drift tube 4 that is, they extend axially along the inner surface of the outer cylinder 30 , The conductive stripes 33 . 34 and 35 extend axially over substantially the same axial length as the spiral resistance strip 70 , The Stripes 33 . 34 and 35 equidistant radians about the z or longitudinal axis of the drift tube, and on each strip, in use, a switchable voltage of 1 to 20 V is applied independently to produce a rotating arcuate electric field which will be described in more detail below. It is understood that also a larger number of stripes than the three stripes 33 . 34 and 35 could be provided. Each of the conductive strips described herein, e.g. B. stripes 31 - 35 . 61 , may be present as a continuous strip or as a discontinuous strip, ie in sections. Similarly, the resistance strip 62 as a continuous strip or as a discontinuous strip, ie in sections.

At the exit end of the drift tube 4 ie at the exit end of the outer cylinder 30 , the ions can escape from the drift space 22 via an exit opening 80 escape. Ions passing through the outlet 80 leak, may be subjected to further processing and / or detection. In the embodiment shown is a Leitmultipol 90 downstream of the outlet 80 provided to receive ions as they leave the drift tube. A switchable lock voltage at the opening 80 can be used to pass the ions of desired mobility before passing through the multipole 90 get into further processing and / or detection levels. The outlet opening 80 thus acts as an ion lock, and to this a switchable voltage of 1 to 10V can be applied to selectively allow ions to pass (gate open) or not pass (gate closed). Preferred is as in 8th shown an annular conductive strip 72 further provided as means for opening ions to the ions 80 to lead. At the annular conductive strip 72 A switchable voltage of 5 to 50V is applied to selectively allow ions to pass therethrough (gate open) or not pass (gate closed).

Below are various modes of operation of the spectrometer 2 described.

Ions can enter the spectrometer 2 be introduced as follows. After ion generation in an ion source (not shown) and optionally any pre-processing of the ions, such as. As ion storage, mass filtering and / or fragmentation, the ions on the Injektultmultipol 10 directed into the spectrometer for injection. For injecting the voltage of the inlet opening or the gate 20 (eg, zero or low) to allow the ions to pass through and the ions into the storage space 21 enter, that is, in the example, the annular volume between the storage section 30 ' and the inner electrode assembly 40 extending axially between the inlet opening 20 and the conductive strip or gate 61 located. The ions can leave the storage space 21 drift out when on the conductive strip 61 that as a lock from the storage room 21 acts, a gate voltage of 5 to 50 V is turned off and at the same voltage as the beginning of the strip 62 is set, allowing ions from the storage space 21 in the drift room 22 due to the axial field caused by the voltage drop between the strips 31 and 32 and along the strip 62 is generated, can drift. The ions then start, through the drift space 22 pass therethrough.

In one mode, called a pass mode, the ions can travel along the drift tube 4 through the drift space 22 drift, attracted by an axial field, ie from the resistance strip 62 to which a voltage of 50 to 200 V is applied but with limited ion mobility separation. In other words, the spectrometer thus acts rather as a simple ionic conductor in this mode. In the pass-through mode, the ions are typically not stored and from the memory space 21 instead, they are continuously transmitted through the spectrometer 2 and its drift tube 4 pass through. Accordingly, the drift tube 4 either be filled with gas at significant pressure for ion mobility separation, or under high vacuum. Because the strip 62 is spiral, the ions are always subject to a small axial field through the drift tube 4 Regardless of where around the inner electrode assembly 4 the ions are around. The ions become radial by applying a DC differential of 2 to 20 V between the resistor outer cylinder 30 and the electrode assembly 40 limited by z. B. to the resistance strip 62 another DC voltage is applied than at the resistance outer cylinder 30 , For example, to the resistance strip 62 a more negative DC voltage can be applied than at the resistance outer cylinder 30 to radially confine positively charged ions (and vice versa). As the ions travel axially through the drift tube, the ions are prevented from contacting the internal electrode assembly 40 colliding by applying an RF voltage of 200 to 1000 V at 3 MHz to the RF electrodes as described above. In this transmission mode, the spiral resistance strip is used 70 a voltage applied to the voltages on the strip 62 is matched so that there is substantially no spiral potential barrier that affects the axial motion of the ions, and instead a smooth linear axial field component is obtained. Accordingly, the ions drift axially through the drift tube 4 in a substantially straight way (they are not subject to diversification). The ions are in an arcuate direction near z. B. the electrode 33 confined by placing higher voltages on the electrodes 34 and 35 be created. In other words, the transmission mode of operation provides that ions travel in a non-spiral straight path through the drift tube 4 drift. The ions may reach the exit opening 80 to which a voltage is applied in the pass-through mode to allow the ions from the drift tube to pass through the multipole as well 90 for optional further processing in any downstream devices (not shown), e.g. As one or more mass filters and / or ion traps, and detection.

In the low-resolution ion mobility separation mode of operation, which has a similar resolution of ion mobility separation as existing straight-line ion mobility spectrometers, the spectrometer becomes 2 operated in the manner of the pass-through mode, except that the ions do not flow continuously through the spectrometer, but instead the ions are stored and as a pulse into the drift tube 4 be released. This can be done by first placing the ions in the storage space 21 introduced as described above. For introducing ions into the storage space, the axial field gradient in the storage space is preferred 21 , z. B. of the strips 31 . 32 , applied to assist the drifting of ions in the storage space. In an operating mode for ion injection into the drift tube is attached to the conductive strip 61 , which gates out of the storage space 21 acts, initially applied a voltage of 5 to 50 V, which is set so that the ions are stopped thereby and thus in the storage space 21 be caught and stored. Having ions in the storage space 21 can enter, in addition to the inlet opening 20 an additional voltage of a few volts may be applied to trap ions in the storage space and also prevent the entry of further ions into the storage space of the device 10 to prevent her. Once the ions in the storage space 21 Although not necessary, it is possible to turn off the axial gradient in the storage space so that the ions in the storage space are stopped. In this mode of operation, it may not be necessary for the inlet electrode 21 the effect is to stop the ions because of the absence of the axial gradient in the storage space 21 itself may be sufficient to stop the ions in the storage space. When applying a lock pulse to the strip 21 and / or upon application of the axial field gradient in the storage space 21 can store the stored ions from the storage space 21 in the drift room 22 drift, z. B. by the axial field caused by the voltage drop between the strips 31 and 32 is produced.

The ion pulse then begins to pass through the drift space 22 as above, and the ions are separated by ion mobility as they travel through the drift space. In this mode, a gas for ion mobility separation occupies the drift space 22 , The gas may be at atmospheric pressure or reduced pressure, preferably 0.005 to 20 mbar, more preferably 0.1 to 1 mbar. The axial field within the drift tube and the drift space 22 in turn is generated by the voltage at the spiral resistance strip 62 and optionally to the outer resistance cylinder 30 is created. Radial restriction and the application of the RF voltage occur in the manner described above for the transmission mode. In this low-resolution mode, the spiral resistance strip is used 70 a voltage applied to the voltages on the strip 62 so that there is essentially no spiral potential barrier which affects the axial movement of the ions. Accordingly drift in this low-resolution Ion mobility disconnect the ions axially through the drift tube 4 and its drift space 22 on an approximately straight path (subject to some dispersion), ie between the inlet 20 and the exit opening 80 , In other words, the low resolution ion mobility separation mode provides that the ions pass through the drift tube 4 drifting in a non-spiral way. The drift time through the drift tube in the low resolution mode may typically be a few milliseconds. After separation according to the ion mobility, the ions reach the exit opening 80 to which a switchable extraction voltage of 1 to 10 V is applied in order to remove the ions from the drift tube through the outlet opening. When the outlet opening 80 is set so that the ions from the drift tube 4 through the multipole 90 Thus, the ions separated according to their ion mobility may optionally be directed to one or more further stages of processing and detection. For example, the ions may be directed to any downstream devices (not shown), e.g. B. to one or more mass filters and / or ion traps and detection. The outlet opening 80 can be operated with a switchable voltage to only pass ions of desired ion mobility to the other stages. Accordingly, the ions can pass through the exit opening 80 either in a static (ie continuous) mode, or an extraction voltage is applied to the exit port continuously, or in a pulsed mode where an extraction voltage is at the exit port 80 is pulsed to allow pulsed extraction to select a particular mobility value or specific mobility values.

The spectrometer of the present invention may also be operated in a high resolution ion mobility separation mode or, in particular, a variety of high resolution modes, as described in detail below, providing a higher resolution for ion mobility separation than the low resolution mode described above. While the low resolution mode uses a straight path through the drift tube, the high resolution mode uses a spiral path through the drift tube. Accordingly, in the case of the high resolution mode, the separation path is longer to permit greater separation of ions for ion mobility. The resolution of the high-resolution mode can accordingly be higher than for a conventional Gradweg ion mobility spectrometer with the same overall dimensions of the drift tube. For example, for a gap of 5mm and diameter 50mm, a gain in separation length> 15 to 30 could be achieved compared to the low resolution mode, and therefore a factor x4 to x5 in gain in resolution. Alternatively, this increase could be achieved by switching to a lower operating pressure (and thus a lower electric field strength, E). Low operating pressures can z. B. be favorable when an ion mobility spectrometer is connected to a mass spectrometer, which requires a high vacuum. The drift time through the drift tube 4 in the high resolution mode may typically be between a few milliseconds to a few tens of milliseconds, depending on the pressures and voltages.

In high-resolution mode, the spectrometer becomes 2 for injecting ions and storing and releasing the ion pulse from the storage space 21 operated in the manner described above (for the low-resolution mode). The ion pulse then begins transmission through the drift space 22 to separate ions for ion mobility as they travel through the drift space. In this mode there is a gas for ion mobility separation in the drift space 22 , The axial field for moving the ions from the entrance end of the drift tube 4 to the exit end of the tube through the drift space 22 again through the at the spiral resistance strip 62 and optionally to the outer resistance cylinder 30 applied voltage generated. The radial confinement including to the wires 50 applied RF voltage is again in the manner described above. However, in the high-resolution mode, unlike the low-resolution mode, the voltage of the conductive electrode or the spiral resistor strip becomes 30 increased to 2 to 20 V, so that there is a spiral electric potential barrier which limits a pure axial movement of the ions, as will now be explained in more detail.

The potential barrier caused by the voltage across the spiral resistance strip 70 is generated in the 3 and 4 represented by the DC profile representations. 3 shows the DC voltage or potential as a function of the z-coordinate, ie in the axial direction along the longitudinal axis of the spectrometer, for fixed radial arc positions (ie, fixed r and φ coordinates). The positions P1 and P2 in the z or axial direction respectively correspond to the axial positions of the entrance and exit ends of the storage space 21 , ie approximated to the positions of the electrodes 31 and 32 , P1 also marks the axial position of the entrance into the drift tube 4 and the drift room 22 , Position P3 corresponds to the exit from the drift tube 4 and the drift space 22 , The axial positions of the storage space 21 and the separation drift space 21 are shown for further clarity. Evident is a generally downwardly inclined axial potential gradient along z (and thus an electric field gradient). The downwardly inclined axial gradient moves positively charged ions to the exit of the drift tube, and it is understood that by inclining the gradient in the opposite direction, negatively charged ions will instead exit could be moved. The axial potential gradient is substantially linear between P1 and P2, ie within the storage space 21 , due to the potential difference between the electrodes 31 and 32 over the resistance cylinder 30 ' is created. The axial potential gradient between P2 and P3, on the other hand, includes a downwardly sloping axial potential gradient onto which is superimposed a series of potential bumps corresponding to the turns of the helix passing through the spiral conducting electrode or strip 70 be formed. In the axial direction, for a fixed r and φ, the potential increases to a local maximum (ie on the top of a bump, the first one with 102 is designated) at points where the resistance strip 70 is closest (ie where he is on the near side of the cylinder 60 runs). The minima between the humps, whose first with 104 are designated correspond to points in the axial direction above the strip 62 where the resistance strip 70 farthest away.

4 shows the DC voltage or potential profile in the arcuate or angular direction φ for a fixed radial and axial position (ie, fixed r and z coordinates) when the same voltages are applied to the strips 33 to 35 be applied, so that any possible arc-shaped potential distribution only from the strips 62 and 70 comes. It can be seen that the potential increases by the angular direction φ, for fixed r and z, to a local maximum 106 indicated at the point where the resistance strip 70 is closest (ie, where he is on the near side of the cylinder 60 is). The potential around the angular direction φ for fixed r and z drops to a local minimum, with 108 at the point above the strip 62 where the resistance strip 70 farthest away (ie, where he is on the far side of the cylinder 60 is).

When the ions follow the axial field gradient in the axial direction from the storage section 21 away in the drift room 22 move, approach the first potential barrier in the form of the first potential bump 102 in 3 at. This corresponds to the approach to the spiral resistance strips 70 , This potential barrier also corresponds to the maximum 106 on the presentation of 4 , The ions can not cross the barrier and instead follow the lowest potential path through the minimum 108 in 4 is generated and are thus operated in the arc direction φ. The combined axial and arcuate motion results in a helical movement of the ions around the inner electrode assembly 40 around when the ions pass through the resistive strip 70 follow generated potential barrier. As the ions travel on the spiral path, they are separated according to their ion mobility. The spiral movement thus substantially increases the path length of the separation according to the ion mobility, compared to the straight passageway. The resistance strip 70 and thus the potential barrier created thereby ends at the exit from the drift tube, so that the ions eventually exit the outlet 80 reach, to which the switchable extraction voltage is applied and which is operable as described above. When the outlet opening 80 is set so that the ions from the drift tube 40 and through the multipole 90 The ions separated according to their ion mobility may optionally undergo one or more further stages of processing and / or detection, as described above. The outlet opening 80 can be operated with a switchable extraction voltage to only pass ions of a desired ion mobility to the other stages.

The high resolution mode is preferably operated with a rotating arcuate electric field applied in the drift tube. In this case, this is done with the electrodes or strips for an arcuate field 33 - 35 which are operated as the ions move along the spiral path through the drift tube. The conductive stripes 33 - 35 are operated in this mode to apply to them independently 5 to 50 volts so as to generate an operation of the arcuate electric field (ie, a field in the arc direction) to drive ions in the arcuate electric field in the arc direction, ie in the same arc direction as the one they follow in the spiral path. The driving arcuate electric field is preferably provided to have a sector (ie, in the arc direction) of less than 360 °, e.g. B. spans 240 °. This can be achieved by applying appropriate voltages to the strips 33 - 35 be created, ie with the highest voltage on the strip 33 , the lowest one 35 and an intermediate one 34 , However, the driving arcuate field is preferably applied progressively in the arc direction (ie, it moves in the arc direction by progressively applying stresses to the strips 33 - 35 ) so that the arcuate field rotates in the arc direction. The angular or rotational velocity (ie, in the arc direction) of this rotating driving arcuate field is preferably synchronized with the angular or rotational velocity of the ions of the selected ion mobility K, so that the ions travel along the spiral path through the drift tube, whereas ions move one another Ion mobility out of phase with the progressing arcuate field and thus may be slowed or lost in the spectrometer, as described in more detail below. Thus, the ions of the selected ion mobility K become around the inner electrode assembly 40 around (ie around the wires 50 around) in the arcuate field, and they are always subject to the optimum electric field E to drive the ions in the arc direction. For example, ions, that of the internal electrode assembly 40 and the wires 50 are closer to a smaller arcuate field where they are located at a smaller radius r such that they acquire substantially the same angular or rotational velocity as ions coming from the inner electrode assembly 40 and the wires 50 are further away, but subject to a larger arcuate field. Moreover, over the course of several radial oscillations, any difference in angular velocity between ions of the same mobility and similar m / z is averaged out.

The high-resolution mode can be ion-filtered so that only ions of selected ion mobility are transmitted through the spectrometer while other ions are filtered out. In the high-resolution filtering mode, when the driving arcuate electric field applied by the arcuate field electrodes spans a sector of less than 360 ° such that it is e.g. B. spans 240 °, the electric field in the remaining sector, z. B. the remaining 120 °, preferably a defocusing field, so that ions in this remaining sector on the outer walls of the drift tube 4 ie on the outer cylinder 30 , get lost. Preferably, the electric field is in the remaining sector, e.g. B. the remaining 120 °, preferably oriented in the opposite direction, and / or voltages are applied to the strips 33 - 35 (eg, the DC voltage on the strip in the remaining sector is lower than the DC voltage on the inner electrode assembly 40 ) that ions in this remaining sector are subject to a defocusing field (ie from the inner electrode assembly) 40 away) and on the outer cylinder 30 get lost. The DC voltage on the strip in the remaining sector may be e.g. B. be made lower than the common DC voltage to the RF wires 50 and the strip 62 . 70 the inner electrode assembly 40 , The 5 and 6 show the total and DC potential profiles along the radial direction r at a fixed axial (z) position for the sector where the driving arcuate field is present and the sector where the defocusing field exists. In other words, the sector where the driving arcuate field exists is where the ions are in phase with the driving arcuate field, and the sector where the defocusing field exists is where the ions are out of phase with are the driving arcuate field. In the 5 and 6 R1 indicates the surface of the inner electrode assembly 40 , and R2 indicates the position of the outer cylinder 30 , In relation to 5 describing where the driving arcuate field is present, it can be seen that the DC potential distribution (solid line) in the radial direction has the effect of causing the ions to the internal electrode assembly 40 to limit, but the effect of HF on the wires 50 is such that the entire potential distribution (dotted line) actually prevents the ions from reaching the inner electrode assembly 40 to meet. Accordingly, the ions in the radial region between the outer cylinder 30 and the inner electrode assembly 40 limited. In relation to 6 which describes where the defocusing field exists (ie, where the driving arcuate field is not present), it can be seen that the DC potential distribution (solid line) and the entire potential distribution (dotted line) in the radial direction have the effect of the ions radially outward to the outer cylinder 30 so that the ions in this sector are lost on the outer cylinder.

The high resolution mode may alternatively be trapped so that ions having such ion mobility that they are slower than the rotating arcuate electric field nevertheless remain trapped in the drift tube. This mode may be referred to herein as a rotary shaft mode. The ions can remain trapped in the drift tube, e.g. Until the rotational speed of the arcuate field has changed until it corresponds to the rotational velocity of the trapped ions of another selected ion mobility, i. H. after the ions of the first selected ion mobility have passed through the drift tube, and thereafter thereafter pass ions having a further selected ion mobility through the drift tube.

It should be noted that in the above embodiments, ions of different m / z move at different radii because the quasi-potential of the RF field is mass-dependent but the DC potential is not.

In order to improve the tactile cycle of the instrument, injection into the ion mobility spectrometer could occur in the same phase of each successive cycle of the arc field. In this case, trapping is in storage space 21 not necessary and could be replaced simply by the strength of the axial field between electrodes 31 . 32 formed in the memory section, cycled through low and high settings, to inject ions into the drift space 22 of the drift space 4 to pulse.

After the ions through the outlet 80 may be extracted at one or more further stages of ion processing (eg, mass spectrometry, such as mass filtering or Mass analysis, with or without ion fragmentation) and / or detection. After that, in the 1 For example, ions extracted are taken from the ionic conductor 90 in the form of a multipolleiter (preferably a quadrupole) which transfers the ions to a downstream mass spectrometer (in 1 not shown). The ion mobility spectrometer according to the present invention may e.g. In different hybrid instrument configurations, such as IMS / MS or IMS / MS / MS or IMS / (MS) ⁿ , where IMS denotes a stage of the ion mobility spectrometer and MS a stage of mass spectrometry. The stages of mass spectrometry may use one or more types of mass spectrometers, such as: time of flight (TOF), ion trap (eg, 3D ion trap or linear ion trap), magnetic sector, quadrupole, multipole, and Fourier transform mass spectrometer (FTMS), such as FT-ICR or an Orbitrap ^™ mass analyzer. The IMS / MS / MS combinations are preferably about: IMS / Q / trap or IMS / Q / Orbitrap ^™ where trap denotes an ion trap, Q denotes a quadrupole mass filter and Orbitrap ^™ denotes an Orbitrap ^™ mass analyzer. The ion mobility spectrometer according to the present invention is ideal for use with ion trap analyzers, including an Orbitrap ^™ mass analyzer.

7 schematically shows a preferred embodiment of an IMS / MS / MS instrument, wherein the IMS comprises the ion mobility spectrometer according to the present invention. The ion source is preferably a source such as an ESI source or a MALDI source, especially for biological samples, including protein mixtures. The ions introduced into the IMS from the source are separated by the IMS as described herein, e.g. In accordance with either the low resolution or high resolution modes, and then passed into the quadrupole mass filter (Q), which may again be operated as a mass filter or only in RF mode, where no mass filtering occurs. From the quadrupole mass filter, the ions can be directed into a high resolution mass spectrometer, in this example an Orbitrap ^™ mass analyzer. In a known step, the ions are first passed from the quadrupole into a curved linear trap (C trap) for pulsed injection into the Orbitrap ^™ mass analyzer. Optionally, the ions may be sent from the C trap to a collision cell (CC) for fragmentation and the fragmented ions may be returned from the C trap for injection into the Orbitrap ^™ mass analyzer.

Alternatively, the ions exiting the ion mobility spectrometer may be detected by an ion detector positioned after the exit aperture of the ion mobility spectrometer, i. H. without further processing.

In one type of operating mode, a mass spectrometer may be configured to detect ions of selected mobility extracted from the IMS having one or a limited number of m / z values, thereby giving the instrument an ion-specific detector. In a particularly typical mode of operation, a mass spectrum is obtained with a mass spectrometer for any narrow range of ion mobility transmitted by the IMS (i.e., for each ion mobility peak). For this latter mode, extraction of the ions from the MS is preferably pulsed, preferably with a delay between the pulses corresponding to the drift time between the ion mobility peaks. The pulses of extracted ions are then each mass analyzed to generate a mass spectrum, thereby potentially dissolving a single ion mobility peak into its m / z components.

In a preferred mode of operation, the ion mobility spectrometer 2 is operated in high resolution filtering mode, as described above, so as to transmit ions with only a narrow range of ion mobilities K, but with a high duty cycle. In relation to 8th This narrow range of ion mobilities K (ie between the dotted lines in the figure) is shown on a mobility / mass plot of K versus m / z. A subsequent mass analyzer, such as an ion trap, receives the ions in the narrow range of ion mobilities and performs mass analysis, ie, an m / z scan. For example, using the in 7 4, the quadrupole mass filter (Q) is operated only in the RF mode so that it does not mass-filter, and then the ions in the narrow mobility range are stored in the C trap and injected into the Orbitrap ^™ mass analyzer for mass analysis therein. Subsequent scans from the ion mobility spectrometer to transmit further ranges of ion mobilities K are then performed and mass analysis is performed for each mobility scan so that a two-dimensional (2D) mobility / mass plot can be obtained as shown in FIG 8th is shown. Areas of the mobility / mass representation where ion species are detected are shown in the figure with shaded bands. Using the known correlation between K and m / z, as in 8th shown, the analysis speed could be increased by combining different K values in a mass spectrum, e.g. By accumulating ions of different K values in the C trap before they are analyzed together in the Orbitrap ^™ mass analyzer. In addition, as described above, fragmentation in a collision cell could be used to generate fragments of selected ions.

Another preferred method is with respect to 8th shown. In this so-called coupled scan method (linked-scan method) it allows the selection of only ions of a certain type or of certain types, eg. Of selected charge states, which can greatly enhance the dynamic range of analysis of complex mixtures, and avoids the analysis of analytically useless ions (eg, singly charged and polymer ions in the case of peptide mixtures). In this coupled scan method, a mass filter, such as the quadrupole mass filter in FIG 7 , rapidly scanned simultaneously with the mobility scan by the IMS, so that only ions of a defined mobility / mass ratio or those lying on a defined curve on a mobility / mass diagram are allowed to enter the subsequent mass analyzer, such as e.g. In the Orbitrap ^™ analyzer of 7 , Prior to the latter mass analysis step, the ions selected according to the defined mobility / mass ratio are preferably accumulated, more preferably in an ion trap, e.g. B. the C-trap in 7 , The accumulated ions can then be released from the ion trap into the mass analyzer. In 9 For example, a representative mobility / mass ratio is shown between the dotted lines accumulated in the ion trap in a scan. As mentioned, at the end of the scan, all of the accumulated ions can be mass analyzed, e.g. B. injected into the Orbitrap ^™ analyzer and the mass spectrum are detected. In such a process, a high resolution mass spectrum, such as obtained with an Orbitrap ^™ analyzer, can be obtained which contains only ions of interest (e.g., 2- or 3-fold charged ions, or only glycopeptides, etc.), and therefore, the space charge capacity of the trap is fully utilized. Similarly, one or more subsequent scans may be made at other mobility / mass ratios. The mass resolution of the mass filter could be selected similar to that of the IMS so that the entire duty cycle remains respectable (eg 1-2%). In order to match the repetition rate of the Orbitrap analyzer, the total scan should take 50 to 1000 ms, depending on the required resolutions in the IMS and quadrupole. In addition, certain selected m / z could be fragmented in an optional collision cell to generate fragments for verification of a corresponding precursor ion.

Of course, there could be other instrument configurations than those in 7 shown configuration may be considered, for. A Q-IMS-TOF configuration, especially such a configuration that contains a cell for fragmenting ions of the same m / z but different mobility. Instead of a quadrupole, other fast mass selectors could be used, e.g. Based on resonance separation on time of flight, as in the co-pending applications with the application numbers GB 1020038.4 and GB 1020039.2 described by the applicant.

It is understood, in view of the principle of operation of the present invention, that the spectrometer could be constructed opposite to the particular preferred embodiment shown, ie with one on the inner surface of the outer electrode 30 arranged sprialigen electrode 70 and radially inward thereof, but RF electrodes disposed near the inner surface of this outer electrode 50 , The electrodes for an arcuate field 33 - 35 could in this case be on the surface of the inner electrode assembly 40 to be ordered. In such embodiments, the direction of the DC field in the radial direction would have to be reversed with respect to that described.

11 Figure 4 shows another embodiment of the present invention providing DC-only isolation of ions. In this embodiment, the electrodes are for a curved field 33 - 35 is replaced by a spiral potential well generated by inner and outer spiral electrodes, as described below. In this case both inner and outer cylinders are included 30 and 40 the double helix arrangement of the resistor strips 62 . 70 on dielectric cylinders, where DC potential distributions are formed along the coils when appropriate voltages are applied to the strips. The outer cylinder 30 in this case comprises a dielectric material on the inner surface of the strips 62 ' . 70 ' are arranged to the inner cylinder 40 indicative. On the outer surface of the inner cylinder 40 in this case are the stripes 62 . 70 trained pointing to the outer cylinder. The inner cylinder 30 is hollow, as shown, although this need not be the case, as explained below. As in the above remarks, one of the spiral strips 62 . 70 ( 62 ' . 70 ' ) in each cylinder a voltage is applied, which is increased relative to the other strip, so that ions can only move along the formed potential valley. To provide an RF trap, an RF voltage is applied to the inner resistive strips 62 . 70 from a metal RF electrode 200 coupled across distributed capacitances of a few hundred pF in the small gap (a few mm) between the RF electrode and the resistive strip 62 . 70 is formed. The RF electrode 200 could be in the dielectric of the inner cylinder 40 embedded or vacuum-insulated therefrom (as shown), and an RF voltage having an amplitude of 200 to 2000 V and a frequency of 3 to 6 MHz is applied thereto. A radial trap could be created either by applying a bias to the outer strips 62 ' . 70 ' relative to the corresponding inner stripes 62 . 70 , (so that the mass-dependent effective potential of 5 is formed), or by coupling similar HF to the external electrodes 62 ' . 70 ' , The gap between the strips 62 and 70 , especially on the inner cylinder, should be minimized to reduce the ingress of DC voltage from the RF electrode into the ion mobility separation (IMS) region (drift space). As an example of construction, a thin sheet of lead silicate glass could be hydrogen-reduced to give a thin conductive film on the outside, and then laser ablation could be used to cut a spiral groove through this layer, thereby forming a very high or high density double helix To form infinite resistance between the windings. Alternatively, a metal RF electrode could be coated with insulating plastic (eg, PTFE or polycarbonate), and then a conductive plastic shield is pressed thereon and then cut (but only partially by the insulating plastic) by laser to form spiral strips. The outer stripes 62 ' . 70 ' could have a greater separation since no RF shielding is required there, and instead would allow the DC field to be attached to the outer resistive coating 240 into the IMS volume for the purposes described below.

If the radial stress differential along the overall length of the device were to be kept constant, this means that the arc field would be inversely proportional to the radius. Therefore, the relative variation of the field over the size of the ion beam should be minimized, either by reducing the beam size for better focusing or reducing the variation to use a larger radius (the latter reduces the quasi-potential of the RF field). For the drift tube dimensions given above (50 mm outer diameter of the inner cylinder and 60 mm inner diameter of the outer cylinder), IMS resolution powers above 100 to 200 are practicable. In order to avoid electrical breakdown due to significant voltage differential between the ends of the gas-filled IMS tube, which could reach as high as hundreds of volts or, if higher resolving power is desired, even thousands of volts, the IMS should always be operated below the breakdown threshold as determined by the Paschen Curve, preferably above 10 ^-2 mbar · m. Fortunately, stress extremes strike the opposite ends of the IMS pipe so that the characteristic size of L could be used (in our case 200 mm). Then, at 2 mbar pressure, the maximum voltage should remain below 2000 V for nitrogen and 600 V for helium, which is already practical for high resolution powers according to Equation 2. It is also important to observe that the RF voltages across the gap also remain below the Paschen curve, preferably below a few hundred volts.

In operation, ions from the injection multipole become 10 in the RF only memory device 230 then the voltage offset in this memory device is raised above the increased voltage at the front of the IMS tube, and thereby the ions are injected into the IMS tube by adjusting the voltage at the inlet port 260 is reduced. This "energy boost" allows both the ion source and subsequent mass analyzers to be held at lower voltage offsets relative to ground.

In high-resolution mode, tensions between the strips 62 and 70 on the inner cylinder 40 and between their counterparts 62 ' and 70 ' on the outer cylinder according to 3 held such that axial electric fields ions from adjacent windings of the strip 70 to the strip 62 to press. The ions find themselves in a spiral potential well, causing them to follow the electric field lines along the spiral path between the inner and outer cylinders. Effective path lengths of up to several meters over a voltage drop of a few kV can be achieved in this mode.

In low resolution mode, the voltage offset of the strip becomes 70 reduced, so that there is no barrier, but instead a linear axial stress distribution between it and the strip 62 is formed, thereby forcing the ions straight along the drift tube of the IMS. An additional axial field is created by passing along the outer coating 240 a voltage is applied. The arcuate electric field still forces the ions to rotate about the axis of the inner cylinder, but in this case the spiral stage is much longer and the run time is shorter. By suitable design of the outer coating 240 and supplying sufficiently high voltages, the arc field within the IMS could be reduced to zero so that the ions travel substantially straight from the input to the output.

In pass-through mode, the operation is similar to the low resolution, but here becomes the RF memory 230 operated at the highest possible frequency between filling and releasing ion packets in cycles (e.g., 200-500 times per second) so that high ion currents can be transmitted up to 10 ⁹ -10 ¹⁰ ions per second. This requires that the pressure in the RF memory exceeds 10 ^-2 mbar. Alternatively, the DC voltage could be along the strips 62 . 70 be reduced to a few tens of volts, and therefore, such an "energy boost" in the ion storage is not necessary, ie ion flow could pass continuously.

It is understood that the ion mobility spectrometer of the present invention could also be used for so-called field asymmetric IMS (FAIMS). Accordingly, the ion mobility spectrometer of the present invention may include a field asymmetric ion mobility spectrometer. For this purpose, it is sufficient to increase the electric field / pressure ratio E / P significantly above 200 V / (m · mbar), preferably above 1000 V / (m · mbar). Alternatively, RF could be made asymmetric on the wires, resulting in additional net displacement of ions in the field. This, in turn, moves ions from their optimal position to another radius, where they maintain a different rate of drift, get out of phase with the rotating arc-shaped electric field, and get lost at the inner or outer electrodes.

The data dependent detection could then be used by the present invention to select between different modes of operation (i.e., the ones indicated above and others) depending on results coming from a mass spectrometric detector in real time. For example, a broad mass range overview spectrum could be used to select m / z of interest for IMS analysis and fragmentation so that MS / MS spectra of selected isomers could be captured.

Advantages of the invention include the ability to switch between different modes of operation, e.g. From fast-pass (ion) or low-pass IMS to various high-resolution IMS modes, such as a high-resolution dual-scan IMS-MS mode. The invention enables high resolution ion mobility filtering in the rotating field. The invention allows for a spiral path, thereby saving space for a high resolution ion mobility separator, but within a straight drift tube, which provides for a simple construction.

It should be understood that the present invention could also operate in a multiplexed mode when more than one ion packet is injected during mobility separation. Hadamard and pseudorandom coding could be used with appropriate unfolding of the resulting data.

As used herein, the term straight means generally or substantially straight, not necessarily strictly, geometrically or mathematically straight, and the term spiral used herein means generally or substantially spirally, not necessarily strictly, geometrically or mathematically spirally. It is understood that it is z. For example, it is not essential that elements of the present invention be strictly, geometrically or mathematically straight or strict, geometrically or mathematically spirally, as might be the case for the invention to work.

As used herein, including in the claims, unless the context indicates otherwise, singular forms of the terms herein should be understood to include the plural form, and vice versa. For example, unless the context indicates otherwise, a singular reference herein, including in the claims such as "a" or "an", means "a" or "more."

Throughout the specification and claims of this specification, the words "comprise", "including", "having" and "containing" and variants of the words, for example, "comprising" and "comprising", etc. include "including, but not limited to". , and should not exclude other components (and do not).

It should be understood that variations of the foregoing embodiment of the invention may be made while still falling within the scope of the invention. Any feature disclosed in this specification, unless otherwise specified, could be replaced by alternative features serving the same or equivalent purposes. Thus, unless otherwise stated, each feature disclosed is an example of a generic series of equivalents or similar features.

The use of any and all examples, or exemplary language ("for example", "such as", and similar expressions) provided herein are merely to aid in illustrating the invention and not to limit the scope of the invention, as long as not otherwise claimed. No term in the specification should be understood as indicating any unclaimed element that is essential to the practice of the invention.

Any steps described in this specification may be performed in any order or concurrently unless otherwise specified or required by the context.

All features disclosed in this specification may be combined in any combination except combinations where at least some of these features and / or steps are mutually exclusive. In particular, the preferred features of the invention are applicable to all aspects of the invention and may be used in any combination. Similarly, features described in non-essential combinations may be used separately (not in combination).

There is provided an ion mobility spectrometer for separating ions according to their ion mobility, comprising in various aspects: a drift tube having a drift space therein and at least two ion separation paths of different lengths in the drift space; a straight drift tube having therein a spiral ion separation path; a spiral ion separation path surrounding an axially extending internal electrode assembly; and a drift tube for separating ions according to their ion mobility, wherein a rotating arcuate electric field is applied in operation to separate ions having an ion mobility such that their rotational speed in the drift tube is matched to the rotational speed of the rotating arcuate field. Also, various methods are disclosed for separating ions according to their ion mobility.

Claims (18)

Ion mobility spectrometer for separating ions according to their ion mobility, comprising a straight drift tube ( 4 ), which contains a drift space ( 22 ) and at least one spiral guide electrode ( 70 ), wherein the drift space ( 22 ) comprises at least two ion separation paths of different lengths, the at least two ion separation paths comprising a first ion separation path which is straight and a second ion separation path which is spiral, and to which the at least one spiral guidance electrode 70 ), a switchable voltage for turning on or off a Leitpotentialbarriere can be applied, so that the ions follow the spiral ion separation path with the Leitpotentialbarriere switched off the straight Ionentrennweg and switched on Leitpotentialbarriere. Ion mobility spectrometer according to claim 1, wherein the drift tube ( 4 ) an axially extending outer electrode assembly ( 30 ) and an axially extending inner electrode assembly ( 40 ), wherein the outer electrode assembly ( 30 ) the inner electrode assembly ( 40 ) surrounds annularly and wherein the drift space ( 22 ) an annular drift space ( 22 ) located between the outer electrode assembly ( 30 ) and the inner electrode assembly ( 40 ) is defined. Ion mobility spectrometer according to claim 1, wherein the drift tube ( 4 ) axially extending RF electrodes ( 50 ), which are spaced apart annularly about the axis of the drift tube (FIG. 4 ) are arranged around, to ions in the drift tube ( 4 ) radially when an RF field in the drift tube ( 4 ) by means of the HF electrodes ( 50 ) is created. An ion mobility spectrometer according to claim 3, wherein the RF electrodes ( 50 ) are spaced apart annularly about an inner electrode assembly ( 40 ) are arranged around, so that the ion separation paths radially outward of the RF electrodes ( 50 ) and wherein the drift tube ( 4 ) has a radial DC field for further radially confining the ions. Ion mobility spectrometer according to claim 2, wherein the drift tube ( 4 ) one or more RF electrodes ( 50 ) associated with the inner electrode assembly ( 40 ) and / or the outer electrode assembly ( 30 ) are coupled to an RF field in the drift tube (FIG. 4 ) in combination with a radial DC field for radially confining ions in the drift tube (US Pat. 4 ). An ion mobility spectrometer according to claim 1, comprising an axial drive electrode ( 62 ) for applying an axial electric field in the drift space ( 22 ) to remove the ions in the drift tube ( 4 ) to drive axially. An ion mobility spectrometer according to claim 1, wherein said at least one spiral conducting electrode ( 70 ) Part of an internal electrode assembly ( 40 ) and / or an outer electrode assembly ( 30 ). An ion mobility spectrometer according to claim 1, further comprising at least one helical axial drive electrode ( 62 ), wherein the at least one spiral guide electrode ( 70 ) and the at least one spiral axial drive electrode ( 62 ) are arranged to form a double helix. An ion mobility spectrometer according to claim 1, further comprising electrodes for an arcuate one Field ( 33 . 34 . 35 ), which extend axially along the drift tube ( 4 ), wherein the electrodes for an arcuate field ( 33 . 34 . 35 ) about the axis of the drift tube ( 4 ) and each electrode for an arcuate field ( 33 . 34 . 35 ) has a switchable voltage independently applied thereto to thereby generate a rotating arcuate electric field by progressively switching the independent switchable voltages in the form of a transient waveform to the electrodes for an arcuate field ( 33 . 34 . 35 ), wherein the rotational speed of the rotating arcuate field is synchronized with the rotational velocity of ions of selected ion mobility. An ion mobility spectrometer according to claim 9, wherein said of said arcuate field electrodes ( 33 . 34 . 35 ), a sector of less than 360 ° spans, and the electric field in the remaining sector is a defocusing field, so that ions in the remaining sector on a wall of the drift tube ( 4 ) get lost. An ion mobility spectrometer according to claim 1, comprising a pulsed ion injector for releasing ions into the drift tube ( 4 ). An ion mobility spectrometer according to claim 1, comprising an inlet electrode for extracting the separated ions from the drift tube (16). 4 ). An ion mobility spectrometer according to claim 1, which is equipped with a downstream of the ion mobility spectrometer ( 2 ) coupled to an ion mobility scan by the ion mobility spectrometer ( 2 ) is scanned so that only ions of a predetermined mobility / mass ratio or those lying on a predetermined curve on a mobility / mass diagram are selected for subsequent processing or detection. The ion mobility spectrometer of claim 13, comprising an ion trap for accumulating the selected ions prior to mass analysis of the accumulated ions. The ion mobility spectrometer of claim 1, wherein said spiral ion separation path is an axially extending internal electrode assembly ( 40 ) surrounds. Ion mobility spectrometer according to claim 1, wherein the drift tube ( 4 ) an outlet opening ( 80 ) and ions the drift tube ( 4 ) through the outlet opening ( 80 ) after following either the straight ionic separation path or the spiral ionic separation pathway. A method of separating ions according to their ion mobility, comprising: providing a straight drift tube ( 4 ), which contains a drift space ( 22 ) and in the drift space ( 22 ) has at least two ion separation paths of different lengths, one of the ion separation paths being straight and another spiraling; Providing at least one spiral guide electrode ( 70 ) in the drift tube ( 4 ), to which a switchable voltage for switching on or off a Leitpotentialbarriere can be applied, so that the ions follow the straight Ionentrennweg with switched Leitpotentialbarriere and with switched Leitpotentialbarriere the spiral Ionentrennweg; Selecting one of the ionic separation paths to which ions are to follow; and causing the ions to follow the selected ion separation path and separating the ions along the selected ion separation path according to their ion mobility. The method of separating ions of claim 17, wherein said spiral ion separation path is within said drift tube (13) surrounding an axially extending inner electrode assembly. 4 ) provided.

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